1. Field of the Invention
This invention relates to the use of diterpene compounds, in particular hypoestoxides, derivatives and agonists thereof for inhibiting tumor growth.
2. Background Art
The strongest impetus for the many decades of research in tumor biology has been the hope that effective therapeutic agents might be found cytotoxic against tumor cells that could be used for prevention and therapy of cancer.
Malignant melanoma continues to increase in incidence. Currently, malignant melanoma is the fifth most frequently occurring cancer in the U.S. While early melanoma is highly curable by surgical means, the prognosis of patients with more advanced lesions and/or metastatic disease remains poor (Bezwoda, W R; Cancer Treat Rev 1997;23(1):17-34). Conventional chemotherapy with single-agent activity has a low frequency and short duration of response (Cancer Treat Rev 1997; 23(1):17-34); Mayo Clin Proc 1997;72:367-371).
Metastatic renal cell carcinoma (RCC) is highly resistant to the many systemic therapies that have been extensively investigated (Motzer R J et al. Current Problems in Cancer, 1997;21(4):185-232). RCC occurs nearly twice as often in men as in women. Increased availability of improved and highly sophisticated diagnostic methods such as ultrasonography and computed tomography (CT) scanning (Franklin J R et al. Seminars in Urologic Oncology 1996;14(2):208-215) has revealed a steadily rising incidence of RCC. Cervical carcinoma is the most common malignancy among women in developing countries (Morrow C P et al. J Cell Biochem 1995; suppl 23:61-70) and the third most common malignancy of the female genital tract in the Unites States (Miller B A et al. National Cancer Institute; NIH publication 93-2789, 1993).
All of the subsequent technological advances, including high dose rate therapy, treatment planning, new isotopes, new imaging techniques, and new machines, have had no clinically measurable effect on the curability of cervical cancer (Morrow C P et al. J Cell Biochem 1995; suppl 23:61-70).
Because neurotoxicity and chemotherapeutic drug resistance remain some of the major clinical problems associated with failure in the therapy of human cancer (Anticancer Drugs 1995;6(3):369-383; Curr Opin Oncol 1997;9(1):79-87), there is a need for study of new agents with fewer side effects and maximum efficacy.